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Drug Interactions between enzalutamide and Prograf

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

tacrolimus enzalutamide

Applies to: Prograf (tacrolimus) and enzalutamide

MONITOR CLOSELY: Coadministration with potent inducers of CYP450 3A4 and/or P-glycoprotein may significantly decrease the plasma concentrations and pharmacologic effects of tacrolimus. The mechanism probably involves reduced absorption as well as accelerated clearance of tacrolimus due to induction of both intestinal P-glycoprotein drug efflux transporter and hepatic/intestinal CYP450 3A4 isoenzymes. In a study of six healthy volunteers, a potent inducer of CYP450 3A4 and P-gp, rifampin (600 mg daily for 18 days) increased the average clearance of tacrolimus (0.1 mg/kg orally and 0.025 mg/kg/4 hours intravenously) by 47% and decreased its oral bioavailability from 14% to 7%. There have been case reports of transplant patients whose tacrolimus blood levels dropped significantly or became subtherapeutic as early as two days following the initiation of rifampin, subsequently requiring discontinuation of rifampin or substantial increases (up to ten-fold over several months) in tacrolimus dosage.

MANAGEMENT: Given the risk of organ rejection associated with inadequate immunosuppressant levels, caution is advised if tacrolimus must be coadministered with potent inducers of CYP450 3A4 and/or P-gp. Tacrolimus blood levels should be closely monitored and the dosage adjusted accordingly, particularly following initiation or discontinuation of inducer therapy in patients who are stabilized on their anti-rejection regimen.

References

  1. Iwasaki K, Matsuda H, Nagase K, Shiraga T, Tokuma Y, Uchida K (1993) "Effects of twenty-three drugs on the metabolism of FK506 by human liver microsomes." Res Commun Chem Pathol Pharmacol, 82, p. 209-16
  2. (2001) "Product Information. Prograf (tacrolimus)." Fujisawa
  3. Thompson PA, Mosley CA (1996) "Tacrolimus-phenytoin interaction." Ann Pharmacother, 30, p. 544
  4. Furlan V, Perello L, Jacquemin E, Debray D, Taburet AM (1995) "Interactions between FK506 and rifampin or erythromycin in pediatric liver recipients." Transplantation, 59, p. 1217-8
  5. Hebert MF, Fisher RM, Marsh CL, Dressler D, Bekersky I (1999) "Effects of rifampin on tacrolimus pharmacokinetics in healthy volunteers." J Clin Pharmacol, 39, p. 91-6
  6. Moreno M, Latorre A, Manzanares C, et al. (1999) "Clinical management of tacrolimus drug interactions in renal transplant patients." Transplant Proc, 31, p. 2252-3
  7. Chenhsu RY, Loong CC, Chou MH, Lin MF, Yang WC (2000) "Renal allograft dysfunction associated with rifampin-tacrolimus interaction." Ann Pharmacother, 34, p. 27-31
  8. Bhaloo S, Prasad GV (2003) "Severe reduction in tacrolimus levels with rifampin despite multiple cytochrome P450 inhibitors: a case report." Transplant Proc, 35, p. 2449-51
  9. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  10. Cerner Multum, Inc. "Australian Product Information."
View all 10 references

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Drug and food interactions

Moderate

tacrolimus food

Applies to: Prograf (tacrolimus)

ADJUST DOSING INTERVAL: Consumption of food has led to a 27% decrease in the bioavailability of orally administered tacrolimus.

MANAGEMENT: Tacrolimus should be administered at least one hour before or two hours after meals.

GENERALLY AVOID: Grapefruit juice has been reported to increase tacrolimus trough concentrations. Data are limited, but inhibition of the CYP450 enzyme system appears to be involved.

MANAGEMENT: The clinician may want to recommend that the patient avoid ingesting large amounts of grapefruit juice while taking tacrolimus.

References

  1. (2001) "Product Information. Prograf (tacrolimus)." Fujisawa
  2. Hooks MA (1994) "Tacrolimus, a new immunosuppressant--a review of the literature." Ann Pharmacother, 28, p. 501-11

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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